The overall goal of the proposed research is to develop new synthetic methods, involving transition metals, for the synthesis of complex molecules having biological activity, and to demonstrate the efficacy of these methods in the synthesis of a number of important classes of organic compounds. Specific problems to be addressed are: (1) Development of palladium catalyzed olefin-nucleophile, olefin-insertion, and oxidative addition-insertion reactions for the synthesis of mitomycin analogs (pyrroloindoloquinones) and related heterocycles, and ergot alkaloid systems. (2) Development of Pd catalyzed cyclization of Omega olefinic tosamides for the synthesis of tropanes, mesembrines, tetrahydroisoquinolines, oxa- and carbacephams, and other unsaturated carbocyclic systems. (3) Development of the Pd assisted alkylation of olefins for the synthesis of prostaglandins, prostacyclins, steroids, and other carbocyclic systems. (4) Initiation of a study of the reactions of early transition-metal carbenes with imines to form Betal-lactams or 3-azetidinones. A number of new synthetic methods will be explored and developed, with the intent of developing general synthetic approaches to biologerally active classes of compounds. These methods are designed to permit systematic structural variation to maximize activity.